Evaluation of Primary Chronic Autonomic Failure

NCT00059033 | Terminated

• 2 other identifiers: 03000403-N-0004
• Study Type: observational
• Target: 325
• Locations: 1 country
• Sites: 1

Brief Summary

This study will conduct tests in patients with primary chronic autonomic failure (CAF) to learn more about these disorders, which include pure autonomic failure, multiple system atrophy, Parkinson's disease with autonomic failure, and autoimmune autonomic neuropathy. Healthy volunteers and patients with primary CAF 18 years of age or older may be eligible for this study. Participants undergo some of the following tests:

• Blood studies, including arterial catheter insertion to measure blood pressure and collect arterial blood samples, blood flow studies using sensors applied to the skin and a pressure cuff around a limb, and blood draw for genetic studies.
• Bladder motility: Ultrasound test of bladder function.
• Electrocardiogram and heart ultrasound.
• Responses to changes in temperature: Warm water and then room temperature water are passed through watertight pads applied to the back and front of the body and body temperatures are measured.
• Gastrointestinal motility: Bowel sounds are recorded using a microphone placed on the abdomen.
• Lower body negative pressure: The lower body is placed into an airtight barrel-like chamber. Some air is sucked out of the barrel, causing blood to pool in the legs, as occurs during standing.
• Lumbar puncture: A needle is inserted in the space between the bones in the lower back to collect a small sample of cerebrospinal fluid.
• Microdialysis to measures levels of chemicals in the body fluid of certain tissues. A solution is passed through a thin tube inserted into the skin. Chemicals in the body tissues enter the solution. The solution is collected and the chemical levels are measured.
• PET scanning: A nuclear medicine test to produce images of body organs. For patients with urinary problems, a catheter is inserted into the bladder before starting the scan.
• Pupillometry: The pupil of the eye is measured using a special camera in a light-controlled room.
• QSART. A small amount of a brain chemical is applied to the skin with a tiny amount of electricity, and the sweat in a nearby patch of skin is measured.
• Measurement of saliva production, using a cotton-like material placed between the teeth and gums to absorb saliva.
• Skin electrical conduction test, using sensors on the skin to measure sweat production.
• Skin and core temperature measurements using sensors on the skin and in the ear canal.
• Speech and swallowing assessment for patients with speech and swallowing difficulties.
• Stress echocardiogram: A catheter is placed in the subject's arm for sampling blood or giving a drug while the subject exercises. During the test, blood pressure, pulse rate, and EKG are continuously monitored.

Conditions

Autonomic Nervous System Diseases

Keywords

6-[18F]Fluorodopamine; Autonomic Failure; Parkinson's Disease; Multiple System Atrophy; Pure Autonomic Failure; Primary Chronic Autonomic Failure; CAF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects are patients with known or suspected primary CAF, based on referral information and confirmation of the clinical diagnosis at the intake evaluation. They are classified by results of the intake evaluation and then undergo comprehensive autonomic function testing.
• Patients with primary or iatrogenic CAF are included. Control patients have been previously diagnosed with PD or MSA without OH, confirmed at the time of the intake evaluation.
• Healthy Volunteers 18 years old or older are included. People at increased risk for PD or CAF consent in this study as if they were patients (e.g., to enable DNA extraction and storage).
• All subjects must be able to provide their own consent to participate or have an existing Durable Power of Attorney (DPA) in place.

You may not qualify if:

• Age: People younger than 18 years old are excluded.
• Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.
• Disqualifying Conditions A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are hepatic or renal failure (defined by serum creatinine more than 1.5 g/dL), symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, and symptomatic coronary heart disease. Patients are excluded from further participation if the results of the intake evaluation lead to a diagnosis of a secondary form of CAF, such diabetic autonomic neuropathy. Candidate subjects who are unable to give their own consent and who do not have an existing DPA in place are excluded. Pregnant or lactating women are excluded from the study.
• Medications Patients with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Patients are not to discontinue any medications before the patient or the patient s doctor discusses this with the Principal Investigator, Research Nurse, or Nurse Practitioner. If it is decided that discontinuing medications would be unsafe, then the patient may be excluded from all or part of the study.
• Herbal Medicines and Dietary Supplements Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements may be disallowed before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
• Practical Limitations Patients in whom we feel it would be difficult to insert a catheter into a vein may be excluded. Subjects who are not expected clinically to tolerate lying still during the procedures may be excluded.
• Pregnancy Pregnant or lactating women are excluded from the protocol overall. In women with child-bearing potential, blood testing for pregnancy will be done with 24 hours before initial testing (except for obtaining the medical history and physical examination) or any testing involving radioactivity under the protocol. Repeat pregnancy testing will be done before any procedure or drug administration under the protocol that takes place more than one week from a previous pregnancy test. Participants will not start or remain in the study if pregnancy test is positive.
• Refusal to Undergo Certain Procedures Candidate subjects are excluded if they refuse to undergo certain procedures. These are: (1) IV catheter; (2) electrocardiogram; (3) blood drawing; (4) DNA extraction and storage (patients and non-HV controls only); and (5) DNA analysis (patients and non-HV controls only).

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Klockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G. Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin Auton Res. 1998 Dec;8(6):359-62. doi: 10.1007/BF02309628.

  PMID: 9869555 BACKGROUND

• Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997 Apr 2;277(13):1046-51.

  PMID: 9091692 BACKGROUND

• Reinhardt MJ, Jungling FD, Krause TM, Braune S. Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake. Eur J Nucl Med. 2000 May;27(5):595-600. doi: 10.1007/s002590050548.

  PMID: 10853817 BACKGROUND

MeSH Terms

Conditions

Autonomic Nervous System Diseases; Pure Autonomic Failure; Parkinson Disease; Multiple System Atrophy

Condition Hierarchy (Ancestors)

Nervous System Diseases; Primary Dysautonomias; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• David S Goldstein, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 16, 2003
• First Posted: April 16, 2003
• Study Start: April 10, 2003
• Study Completion: October 30, 2018
• Last Updated: December 12, 2019

Record last verified: 2018-10-30

Locations

US (1)